The functional properties of soft connective tissue are determined by the content and organization of connective tissue cells and extracellular matrix. The connective tissue cells are responsible for the synthesis, organization, and breakdown of the extracellular matrix. Collagen and elastin fibers together comprise the fibrous component of the extracellular matrix and function as the major load-bearing elements for tensile stress. Elastin is a relatively low-modulus material that in some tissues determines the elastic properties at lower strains. Collagen fibers have a higher modulus, are more abundant, and provide most of the tensile strength. In tendons and ligaments, where large tensile forces are transmitted along the longitudinal axis, collagen fibers are densely packed in arrays parallel to the tensile load. In skin and fascia, collagen fibers are more diffusely oriented, although a preferred orientation may exist depending on mechanical demand. Both collagen and elastin fibers are stengthened by intermolecular covalent crosslinks.
The extracellular matrix is also characterized by a non-fibrous component comprised of proteoglycans and glycoproteins. Proteoglycans are composed of a protein core attached to various glycosaminoglycan side chains and contain numerous negatively charged sulfate and carboxyl groups. By their ability to produce high osmotic swelling pressure, these ionized groups are the source of a large component of the compressive modulus in connective tissue. Proteoglycans are found in all connective tissue, but are particularly abundant in cartilage and in segments of tendon that are subjected to large compressive forces.
Ligaments are a highly organized load-bearing connective tissue containing collagen fibers and fibroblasts primarily ordered in a parallel array, giving them a flexible yet strong mechanical character. The fibroblasts, which sparsely populate the ligament, are spindle shaped and form intercellular cytoplasmic connections. The collagen fibers are densely crosslinked and oriented in the direction of the mechanical stress. As a result, ligaments are strongest and stiffest in the direction of the mechanical stress.
Tendons are the connective tissue connecting muscles with mobile structures such as bones, cartilages, ligaments, and fibrous membranes. Tendons are white, glistening fibrous cords of various dimensions and considerable strength. They consist almost entirely of white fibrous tissue and collagen fibrils which are oriented parallel to each other and firmly united together. The larger tendons are supplied with blood vessels and nerves.
Some connective tissue has the ability to repair itself and adapt to changes in mechanical demands. During the normal growth pattern and repair of damaged tissue, cellular activities in connective tissue are greatly accelerated and parallel changes in structure and function are observed. For example, the healing of ligament tissue due to an injury can be divided into three phases: inflammation, matrix and cellular proliferation, and remodeling and maturation. Woo, S. L. Y. and Buckwalter, J. A., Eds., Injury and Repair of the Musculoskeletal Soft Tissues, American Academy of Orthopedic Surgeons, Park Ridge, Ill. (1988). Immediately following the disruption of a ligament, the wound site is rapidly filled with clotting blood. Increased vascular permeability causes serous fluid to accumulate and the surrounding tissue to become edematous. Within a few hours, lymphatic cells migrate into the injury site. Subsequently, numerous fibroblasts appear in the wound bed and produce extracellular scar matrix.
Cell and matrix proliferation results in the formation of a highly vascular granulation tissue between the ends of the torn ligament. The tissue is highly cellular, as shown by histology and DNA content, with fibroblasts being the dominant cell type. Collagen turnover, both in terms of synthesis and degradation peaks in the early part of this phase. The collagen synthesized is predominantly type I. The glycosylaminoglycan content is elevated and the water content is higher than normal.
Under polarized light, the extracellular matrix initially appears disorganized and highly cellular. With time, both the composition and organization of the scar tissue continues to approach that of normal tissue. Further, the mechanical strength of the scar tissue increases during this period in response to the mechanical environment, and in some cases can approach that of uninjured tissue.
Both ligament and tendon injuries to the hand, wrist and knee are common clinical problems. For example, injuries of the knee account for about 60% of the cases. Ligament injuries can be classified into three categories: sprain, overstretching (partial rupture), and rupture. Over 80% of ligament injuries can be treated using non-invasive methods such as rest, ointments, elastic bandage, aspiration, or cast. More severe injuries require surgical treatment involving suturing detached or ruptured components. In these cases, success rates of complete healing and reconstruction range from about 60% for the posterior cruciate ligament to about 16% for the anterior cruciate ligament.
Seriously damaged ligament tissue can be replaced by prosthetics or transplantation of autogenous tissue. Prosthetic ligaments currently being investigated in the United States are the Polyflex.RTM. ligament and the Proplast.RTM. ligament. However, these synthetic, biopolymeric materials have not produced satisfactory long term results.
In addition, transplantation of autogenous tissue and tendon transfers have yielded disappointing results. Autogenous corium grafts for the repair of injured collateral knee joint ligaments result in full restoration of stability for about 60% of all cases. However, for the anterior cruciate ligament, autogenous corium grafting proves to be effective for less than 20% of all cases. The effect of autogenous grafts has the further disadvantage of traumatizing uninjured tissues.
Thus, there is a critical need for the development of a more effective method, technique, and material for the reconstruction or replacement of injured ligaments and other connective tissue, such as tendons, skeletal muscle and cardiac muscle.